Excessive drinking during pregnancy is known to harm the foetus, but estimating the effects of moderate prenatal alcohol consumption is difficult, since mothers who choose to drink may differ systematically from those who do not. This column presents recent research showing that a genetic variant in a maternal alcohol-metabolising gene (ADH1B) is negatively related to prenatal alcohol exposure, and unrelated to any of the background characteristics associated with prenatal drinking. Using this genetic variant as an ‘instrumental variable’, the authors find strong negative effects of prenatal alcohol exposure on child educational achievement.

Related

The US Surgeon General first published a report on drinking during pregnancy in 1981, drawing attention to the link between prenatal alcohol consumption and birth defects (Office of the US Surgeon General 1981). The detrimental effects of excessive drinking during pregnancy are now well-known – it potentially leads to a pattern of mental and physical defects known as Foetal Alcohol Spectrum Disorder. The effects of low-to-moderate drinking, however, are less conclusive, and there is no consensus as to what level of exposure is toxic to the foetus.

Most countries, including the US, advise women to abstain from alcohol during pregnancy. Other countries, such as the UK, recommend women not to drink in the first three months of pregnancy, and if they choose to drink, not to exceed 1–2 units once or twice a week, as “at this low level, there is no evidence of any harm to the unborn baby” (National Institute for Health and Care Excellence 2008). These conflicting recommendations arise from inconsistent findings in observational studies of the correlation between alcohol exposure and child development, including physical and mental health, cognitive and non-cognitive outcomes (for a review, see e.g. Gray and Henderson 2006, Polygenis et al. 1998).

Research challenges

A major problem in estimating the effects of prenatal alcohol consumption is that it is a choice. As such, mothers who choose to drink may be systematically different from mothers who choose not to drink. Indeed, several studies show positive social gradients in alcohol consumption. Higher-educated women are more likely to drink in general (see e.g. Cutler and Lleras-Muney 2010) and to drink during pregnancy (Centers for Disease Control and Prevention 2011, von Hinke Kessler Scholder et al. 2014).

This selection issue clearly shows the difficulty in simply comparing the outcomes of children whose mothers drink to the outcomes of children whose mothers did not drink. In addition, as these mothers may differ in other unobserved (to the researcher) ways, we cannot simply control for a set of background factors and assume that this accounts for all relevant confounders. Furthermore, as it is obviously unethical to design a randomised controlled trial, we have to rely on alternative ways to estimate and identify both the short- and longer-term effects of prenatal alcohol exposure.

We here discuss some of the findings of studies that have used such alternative approaches to identify these effects. Some of these studies have investigated the effects on different outcomes at birth, such as birth weight, the probability of having low birth weight or a preterm birth, and foetal growth. Their study designs try to take account of relevant confounders by:

Comparing the birth outcomes of siblings who were differentially exposed to alcohol in the womb (Wüst 2010);

Exploiting changes in the minimum legal drinking age over time across US states that differentially affected pregnant women’s alcohol consumption (Fertig and Watson 2009, Barreca and Page 2012); and

With the exception of Barreca and Page (2012), they find that prenatal alcohol exposure negatively affects children’s birth outcomes.

Looking at later life outcomes, Nilsson (2008) exploits a Swedish alcohol policy experiment that occurred in the 1960s, which increased alcohol availability in two Swedish counties by allowing grocery stores to sell strong beer. The policy led to a sharp increase in alcohol consumption in the experimental regions, particularly among youths, who were not able to purchase alcohol prior to the experiment. He finds that children conceived just before the policy experiment have substantially lower educational attainment, labour market outcomes, and cognitive ability, compared to the surrounding cohorts; whereas those conceived during the policy experiment are born into less stable families.

New research based on genetics: Mendelian randomisation

In a recent paper, we exploit the fact that genetic markers are randomly allocated, and use a carefully validated (maternal) genetic variant that is associated with decreased alcohol intake to estimate the effect on children’s educational attainment later in life (von Hinke Kessler Scholder et al. 2014). This approach is also known as ‘Mendelian randomisation’ (Davey Smith and Ebrahim 2003; see also Lewis et al. 2012 and Zuccolo et al. 2013). We confirm previous research findings, showing that a genetic variant in a maternal alcohol-metabolising gene (ADH1B) is negatively related to prenatal alcohol exposure, and unrelated to any of the background characteristics that we show to be associated with prenatal drinking. Using this genetic variant as an ‘instrumental variable’, we find strong negative effects of prenatal alcohol exposure on child educational achievement.

Conclusions

In summary, studies that attempt to account for the fact that mothers who drink during pregnancy may be systematically different compared to mothers who do not drink (in both observable and unobservable ways) tend to find that prenatal alcohol exposure is harmful to children. As randomised experiments are obviously unethical and infeasible, these studies are crucial in contributing to our knowledge and understanding of the effects of prenatal alcohol exposure on children’s later life development. Hence, we encourage further research to look into these effects in more detail, replicating these and other analyses in different settings and on different data sources.

References

Barreca, A and E Page (2012), “A pint for a pound? Reevaluating the relationship between minimum drinking age laws and birth outcomes”, Tulane Economics Working Paper 1220.

Centers for Disease Control and Prevention (2011), “Drinking while pregnant still a problem”, 13 September.